Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Vinorelbine and epirubicin in metastatic breast cancer. A dose finding study.

The aim of the study was to define the maximum tolerated dose (MTD) of vinorelbine given as one or two weekly doses in combination with epirubicin 60 mg/m2 every third week. The MTD was defined as the dose resulting in a WHO grade III or IV leucopenia exceeding 50% of patients. Patients were treated in groups of 10 at escalating doses of vinorelbine. The number of patients at the final dose level was expanded to 20. The dose of epirubicin was kept constant at 60 mg/m2 every third week. At dose level 1, 15 mg/m2 vinorelbine was given on day 1 at level 2, 20 mg/m2 was given on day 1 and at level 3, 20 mg/m2 was given on days 1 and 8. The MTD was reached at dose level 3. WHO haematological toxicity grade IV occurred in 0, 10 and 45% and grade III at 60, 30 and 30% of patients at dose levels 1, 2 and 3, respectively. Despite the common occurrence of grade IV haematological toxicity, only two serious infections were noted. Non-haematological toxicity of vinorelbine included neurotoxicity, manifesting as muscle weakness, constipation and paresthesias in the majority of patients. Neurotoxicity was usually mild and did not require treatment discontinuation. Phlebitis at the injection site was troublesome in many patients. Alopecia and nausea, probably due to epirubicin, occurred in most patients. The response rates were 22% (95% CI (confidence interval) 3-60%), 40% (12-74%) and 60% (36-81%) at levels 1, 2 and 3, respectively (non-significant).

Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients.

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.

5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy--a randomised study.

166 patients receiving moderately emetogenic chemotherapy were entered into a randomised prospective study in which the efficacy of single dose ondansetron 8 mg, tropisetron 5 mg and granisetron 3 mg in the prophylaxis of acute vomiting was evaluated. 130 patients were evaluable for analysis. During the 24 h following the start of chemotherapy complete control of vomiting was achieved in 80% [95% confidence interval (CI) 73.1; 86.9] of patients receiving granisetron compared with 75% (95% CI 67.1; 82.1) of those on tropisetron and 69% (95% CI 60.5; 76.5) on ondansetron. The patients experienced significantly fewer failures with granisetron (6.2%, 95% CI 2.1; 10.3) than with either ondansetron (14.6%, 95% CI 8.5; 20.6) or tropisetron (13.8%, 95% CI 7.9; 19.7). When asked, 34 (26%) patients out of 130 expressed no preference, 54 (42%) preferred granisetron, 22 (17%) preferred ondansetron and 20 (15%) preferred tropisetron. All the 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy. The observed differences in the control of emesis, although statistically significant, may not have clinical significance.

Comparison of DNA and karyotype aneuploidy in malignant lymphomas.

Tumors from 48 patients with non-Hodgkin's lymphoma were examined for flow cytometric DNA ploidy and chromosome constitution to determine the degree of concordance of these two methods. Histologically, there were 24 low-grade, 19 intermediate, and 5 high-grade lymphomas. Flow cytometry revealed an aneuploid cell population in 19% of the cases. The mean DNA index of the aneuploid tumors was 1.58 +/- 0.71. The frequency of DNA aneuploidy was only slightly higher (23%) in intermediate than in low-grade lymphomas (17%). None of the five high-grade lymphomas showed DNA aneuploidy. The chromosome study was successful in 81% of cases (39 of 48), and clonal chromosome abnormalities were observed in 92% of these (36 of 39). In most of the chromosomally abnormal clones the chromosome number was in the diploid range. Most tumors with pseudodiploid (46 chromosomes), hypodiploid (45-44 chromosomes), or hyperdiploid (47-49 chromosomes) clones were DNA diploid by flow cytometry. On the other hand, all specimens with a chromosome number exceeding 50 were DNA aneuploid by flow cytometry. Therefore, flow cytometric DNA analysis appears to be a rather coarse method that will detect aneuploidy only when there is a major increase in chromosome material.

A method for analysis of cell morphology, banded karyotype, and immunoperoxidase identification of lymphocyte subset on the same cell.

The authors describe a method that allows three staining procedures to be applied to the same mitotic cell, namely Giemsa staining for morphology, immunoperoxidase staining for surface markers, and banding of the chromosomes for karyotype. After culturing of the blood lymphocytes, colchicine was added to arrest the cells in mitosis. After mild hypotonic treatment, the cells were cytocentrifuged to glass slides. The mitotic cells of different lymphatic cell subsets were identified with monoclonal anti-sera against T-helper-, T-suppressor-, and B-cells using the immunoperoxidase technic. The cells were counterstained with Giemsa for morphologic identification. After removal of Giemsa stain and peroxidase, the chromosomes were G-banded.

Immunophenotyping of aneuploid cells.

This review article describes the MAC and MACISH (morphology, antibody, chromosomes, in situ hybridization) methods, which allow the examination of numerical chromosome abnormalities of morphologically and immunologically classified interphase or mitotic cells. Results of studies using these methods indicate that the proportion of mitotic B cells is the same in phytohemagglutinin- and pokeweed mitogen-stimulated lymphocyte cultures, that the proportions of different cell lineages vary greatly after short-term culture of bone marrow cells, that only B cells have a clonal chromosome abnormality in B-cell type chronic lymphatic leukemia and lymphoma, that a clonal chromosome abnormality of patients with T-cell lymphoma may occur in a different T cell subpopulation or at a different maturation stage in certain lineages while B cells show a normal karyotype, that only Reed-Sternberg cells have a clonal chromosome abnormality in Hodgkin's disease, and that in a proportion of patients with acute myeloid leukemia not only a granulocytic-monocytic lineage but also erythrocytic and megakaryocytic lineages show a clonal chromosome abnormality.

Clinical significance of the del(20q) chromosome in hematologic disorders.

Patients with hematologic neoplasias often have chromosomal aberrations in the cells of their bone marrow or unstimulated blood. One recurrent abnormality is a deletion of the long arm of chromosome 20, primarily described in polycythemia vera, but later seen in a range of hematologic disorders. We have studied 32 patients with del(20q) as the sole chromosomal aberration, investigating significance of this aberration for the clinical diagnoses, hematologic parameters, and prognoses within this patient group. According to our results, del(20q) is primarily associated with myeloid disorders, but it is not specific for any certain disease, nor does the proportion of cells with del(20q) correlate with prognosis.

Unique display of a pathologic karyotype in Hodgkin's disease by Reed-Sternberg cells.

The clonality of Reed-Sternberg cells is still a matter of controversy. In Hodgkin's disease, these cells rarely constitute more than 2% of all cells in tissue biopsies of lymph node lesions, the rest being a large collection of various reactive cells. To determine in which cells the abnormal karyotype occurs, we studied two patients with Hodgkin's disease by a cytogenetic method allowing simultaneous analysis of cell morphology, immunologic phenotype, and karyotype in the same mitotic cell. The Ber-H2 (CD30) and Leu-M1 (CD15) monoclonal antibodies were used to identify mitotic Reed-Sternberg cells. In 24-48-hour cultures of lymph node cells from Hodgkin's lesions, there was a mixture of cells with an abnormal clonal karyotype and a normal karyotype. The abnormal clonal karyotype was restricted to Ber-H2- and Leu-M1-positive cells, i.e., the Reed-Sternberg cells. In keeping with these findings, most of the clonal atypical karyotypes occurred in kappa- and lambda-positive large cells, i.e., Reed-Sternberg cells. Mitotic cells with T markers (CD3,4,8) or B markers (CD22) had the normal karyotype. There were no mitoses in cells expressing the antigens recognized by Leu11 (CD16) or Leu11 + Leu7. These findings provide strong evidence suggesting that in Hodgkin's disease only the Reed-Sternberg cells possess a clonal karyotypic abnormality and thus are most probably the only neoplastic component in Hodgkin's disease.

Chromosome abnormalities in 16 Finnish patients with Burkitt's lymphoma or L3 acute lymphocytic leukemia.

Eleven patients with Burkitt's lymphoma (BL), i.e., small noncleaved non-Hodgkin's lymphoma, and 5 patients with Burkitt-type acute lymphocytic leukemia (ALL-L3) were selected for chromosome study. Two of the 16 patients had no B-cell markers, but the erythrocyte marker--glycophorin A--was present on the surface of the leukemic blasts. The critical breakpoint at 8q24 was detected in 14 of the 16 patients, whereas this aberration was not detected in any of the 134 patients belonging to other subgroups of non-Hodgkin's lymphoma or ALL that we studied during the same period. In addition to the t(8;14)(q24;q32), the following translocations with the breakpoint at 8q24 were seen: t(2;8)(p11;q24), t(8;11)(q24;q13) in BL, and t(2;8;14)(p11 or p12;q24;q32) in ALL. Additional aberrations seen more than once were trisomy #7 and abnormalities in chromosomes #1, #11, and #13.

t(2;5) (p23;q35)-A Specific Chromosome Abnormality in Large Cell Anaplastic (Ki-1) Lymphoma.

Chromosome abnormalities of three patients with Ki-1 lymphoma are presented. In order to be included in the study each case fulfilled the following criteria: the majority of the tumour cells were positive for the Ki-1 antigen (CD30), and the cells were large with relatively abundant, slightly basophilic cytoplasm. In all cases, a major proportion of mitoses contained a complicated clonal chromosome abnormality. Two patients had a 2;5 translocation; and the third had break points at 14q32 and 2p12. The latter patient showed expression of B-cell antigens and had rearrangements in the immunoglobulin heavy chain and kappa light chain genes. The two patients with the 2;5 translocation were epithelial membrane antigen positive, but did not exhibit rearrangements of immunoglobulin/T-cell receptor genes or expression of T-/B-cell antigens.

Oral sources of septicaemia in patients with malignancies.

This article reviews papers dealing with oral infections of adult septicaemia patients, searched from MEDLINE, Current Contents and Core Biomedical Collection databases from January 1966 to November 1996. Case reports were excluded. The systematic review of literature revealed that our knowledge of the topic is mostly based on very small patient material. There are no multicentre studies on the effects of various oral health treatment modes on the prevention of septicaemia of oral origin. The number of controlled and comparative studies on the efficacy of the different treatment protocols of oral infections is also small. Current recommendations in this respect are mainly empirical and not evidence based. Clinical practice guidelines are therefore urgently needed. Nevertheless, close co-operation between oncological and oral health units is emphasised because many studies have shown that the oral cavity is indeed an important source of bacteraemia. Life-threatening infections may follow if maintenance of oral health is neglected during anticancer therapy and if potential oral infection foci are left untreated before immunosuppressive therapy.

Five-year follow-up study of saliva, mutans streptococci, lactobacilli and yeast counts in lymphoma patients.

Twenty-two patients out of the 79 that were originally included were examined 5 years after beginning anticancer therapy for lymphomas. The patients' cumulative data on salivary flow rate, buffering capacity and acidogenic microbial counts were compared with respective data of 17 patients who died during the follow-up. Stimulated saliva samples had been taken at baseline and during the cytostatic treatment with combination chemotherapy, and 1 year and 5 years later. Chair-side kits were used at the hospital ward for the assessment of the study parameters. Mean saliva flow at baseline was 1.5 +/- 0.7 ml/min in the surviving group and 1.5 +/- 0.8 ml/min in the deceased. Salivary flow rates were not affected by the anticancer treatment and there was no statistically significant difference between the groups in this respect. A significant difference was observed between the groups in salivary buffering capacity values at baseline: only 32% of the survived had low buffering capacity in comparison to 69% of those who later died (P < 0.02). Buffering capacity values remained low in 50% of the surviving patients 5 years later. Higher mutans streptococci and lactobacilli counts were seen among the deceased than in the survived patients but mutans streptococci decreased significantly in both groups after the start of the anticancer therapy (P < 0.05). The number of positive yeast counts increased consistently during the chemotherapy in both groups, being higher in the survived when compared with the deceased patients. Yeast counts remained positive 5 years later in 73% of the survived patients, while the mean mutans streptococci and lactobacilli counts decreased below baseline values. The results showed that persistently high salivary microbial counts and low buffering capacity may be linked with poor prognosis.

Five-year follow-up of saliva in patients treated for lymphomas.

OBJECTIVE: Patients treated for Hodgkin's disease and non-Hodgkin lymphomas were followed for 5 years after start of therapy. The patients received combinations of anticancer drugs for curative intent for 6 months (Hodgkin's disease) or 7 months (non-Hodgkin lymphomas). STUDY DESIGN: Cumulated data of 22 surviving patients (mean age, 49 years) were compared with that of 17 patients (mean age, 52 years) who had died or were terminally ill at the 5-year examination. Saliva samples were taken at baseline, and 4, 6, 12, and 60 months after start of chemotherapy. Salivary flow rate and a variety of biochemical constituents were analyzed. RESULTS: The results showed no long-term effect of anticancer treatment on salivary flow rates. Neither was there any difference between the surviving or deceased patients' baseline values (1.5 +/- 0.7 mL/minute versus 1.5 +/- 0.8 mL/minute) and after chemotherapy. Lysozyme, IgA, IgG, and IgM concentrations decreased after chemotherapy. Significantly lower values were observed at the 5-year examination than at baseline. This was particularly evident in IgA, which is the major immunoglobulin in saliva; mean IgA was 70.5 +/- 52.8 mg/mL at baseline, 35.8 +/- 15.0 mg/mL 5 years later (p < 0.001). Salivary total protein and amylase concentrations were significantly decreased (p < 0.001 and p < 0.05, respectively), whereas albumin concentration was significantly increased at the 5-year examination (p < 0.05). When the salivary biochemical results were compared between the surviving and deceased patients, no statistically significant differences were observed. At baseline, however, the mean immunoglobulin values were lower in patients who later died, in comparison with those who survived. CONCLUSIONS: These results showed that modern anticancer therapy need not cause severe side effects on salivary flow rates and composition. In addition, apart from the long-term immunosuppression, no significant decreases were expressed in salivary defensive factors.

Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up.

BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.

Specificity of haematological indicators for '5q- syndrome' in patients with myelodysplastic syndromes.

83 patients with myelodysplastic syndromes were analyzed for the presence of three haematological features: (1) macrocytic anaemia, (2) normal or high platelet count and (3) megakaryocytic hypolobulation in most megakaryocytes. In 10 of the 83 patients, a 5q- chromosome was the only clonal aberration; 31 patients had other chromosomal aberrations (including 6 patients with 5q- chromosome and other abnormalities in the same clone) and 42 patients had a normal karyotype in their bone marrow cells. 9 patients displayed all three haematological features investigated. In 8 of these patients the 5q- chromosome was the only clonal aberration. The 9th patient had a karyotype of 47,XX, + 8. None of the 6 patients with 5q- chromosome and additional abnormalities in the same clone fulfilled all criteria. The '5q- syndrome', a situation with the 5q- chromosome as a sole aberration, should be accepted as a diagnostic entity within the macrocytic anaemias. This syndrome can be suspected on the basis of the above haematological indicators and the diagnosis confirmed with bone marrow karyotype analysis.

Plasma exchanges in the treatment of rapidly progressive glomerulonephritis associated with chronic dental infection.

A patient is described in whom rapidly progressive, crescentic (in 80% of the glomeruli) glomerulonephritis was associated with chronic dental infection. Eradication of the infection as the sole form of therapy failed to arrest the rapidly advancing renal failure. Institution of plasma exchanges and immunosuppression was accompanied by an abrupt reversal of the renal function and a remission, which until now has lasted for two years.

Empiric treatment of serious infections in patients with cancer: randomised comparison of two combinations.

Infection is the immediate cause of death in many patients with cancer. Traditionally, combinations of modern beta-lactam antibiotics and aminoglycosides are empirically used in the treatment of patients with neutropenia and presumed infection. However, the new quinolones appear to have become potent combination partners for beta-lactams. Eighty-seven patients with presumed serious infection were blindly randomised to receive either 2 g cefotaxime i.v. plus 200 mg ofloxacin twice daily (group 1) or 2 g cefotaxime i.v. twice daily plus tobramycin i.v. three times daily with dosage adjustment according to renal function and body weight (group 2). The response rate was significantly higher in group 1 (71%) compared to group 2 (47%). The cefotaxime/ofloxacin combination proved to be safe and represented a considerable reduction of workload on the nursing staff.

Increased number of functionally defective large granular lymphocytes in lymphoma patients.

50 untreated patients with either Hodgkin's disease or non-Hodgkin lymphoma were studied for natural killer (NK) activity on the single cell level. The non-Hodgkin lymphoma patients had a significantly higher proportion of large granular lymphocytes-cells mediating the natural cell mediated cytotoxicity in humans-among peripheral blood lymphocytes. Yet, the single cell assay in agarose and the standard 51Cr assay revealed a significantly decreased capacity to bind and lyse the K562 target cells. The recycling capacity was also found to be lower in the lymphoma patients' NK cells compared to the healthy controls.